{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:41:35Z","timestamp":1788424895962,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:00:00Z","timestamp":1720742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>GCH1<\/jats:italic> gene encodes the enzyme guanosine triphosphate cyclohydrolase I (GTPCH), which catalyzes the rate\u2010limiting step in the biosynthesis of tetrahydrobiopterin (BH4), a critical cofactor in the production of monoamine neurotransmitters. Autosomal dominant GTPCH (adGTPCH) deficiency\u00a0is the most common cause of dopa\u2010responsive dystonia (DRD), whereas the recessive form (arGTPCH) is an ultrarare and poorly characterized disorder with earlier and more complex presentation that may disrupt neurodevelopmental processes. Here, we delineated the phenotypic spectrum of ARGTPCHD and investigated the predictive value of biochemical and genetic correlates for disease outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim was to study 4 new cases of arGTPCH deficiency and systematically review patients reported in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical, biochemical, and genetic data and treatment response of 45 patients are presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three phenotypes were outlined: (1) early\u2010infantile encephalopathic phenotype with profound disability (24 of 45 patients), (2) dystonia\u2010parkinsonism phenotype with infantile\/early\u2010childhood onset of developmental stagnation\/regression preceding the emergence of movement disorder (7 of 45), and (3) late\u2010onset DRD phenotype (14 of 45). All 3 phenotypes were responsive to pharmacological treatment, which for the first 2 must be initiated early to prevent disabling neurodevelopmental outcomes. A gradient of BH4 defect and genetic variant severity characterizes the 3 clinical subgroups. Hyperphenylalaninemia was not observed in the second and third groups and was associated with a higher likelihood of intellectual disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The clinical spectrum of arGTPCH deficiency is a continuum from early\u2010onset encephalopathies to classical DRD. Genotype and biochemical alterations may allow early diagnosis and predict clinical severity. Early treatment remains critical, especially for the most severe patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.14157","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T02:35:28Z","timestamp":1720838128000},"page":"1072-1084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes"],"prefix":"10.1002","volume":"11","author":[{"given":"Maria","family":"Novelli","sequence":"first","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Department of Human Neurosciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Tolve","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, Department of Experimental Medicine AOU Policlinico Umberto I\u2010Sapienza University  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